- The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol
-
Daptomycin (dap) is an important antibiotic that interacts with the bacterial membrane lipid phosphatidylglycerol (PG) in a calcium-dependent manner. The enantiomer of dap (ent-dap) was synthesized and was found to be 85-fold less active than dap against
- Moreira, Ryan,Taylor, Scott D.
-
-
- Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**
-
Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.
- Cunha, Ana V.,Havenith, Remco W. A.,Holzheimer, Mira,Minnaard, Adriaan J.,Schouten, Stefan,Sinninghe Damsté, Jaap S.
-
supporting information
p. 17504 - 17513
(2021/07/06)
-
- Non-naturally Occurring Regio Isomer of Lysophosphatidylserine Exhibits Potent Agonistic Activity toward G Protein-Coupled Receptors
-
Lysophosphatidylserine (LysoPS), an endogenous ligand of G protein-coupled receptors, consists of l-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages, respectively. An ester linkage of phosphatidylserine can be hydrolyzed at the 1-position or at the 2-position to give 2-acyl lysophospholipid or 1-acyl lysophospholipid, respectively. 2-Acyl lysophospholipid is in nonenzymatic equilibrium with 1-acyl lysophospholipid in vivo. On the other hand, 3-acyl lysophospholipid is not found, at least in mammals, raising the question of whether the reason for this might be that the 3-acyl isomer lacks the biological activities of the other isomers. Here, to test this idea, we designed and synthesized a series of new 3-acyl lysophospholipids. Structure-activity relationship studies of more than 100 "glycol surrogate"derivatives led to the identification of potent and selective agonists for LysoPS receptors GPR34 and P2Y10. Thus, the non-natural 3-acyl compounds are indeed active and appear to be biologically orthogonal with respect to the physiologically relevant 1-and 2-acyl lysophospholipids.
- Nakamura, Sho,Sayama, Misa,Uwamizu, Akiharu,Jung, Sejin,Ikubo, Masaya,Otani, Yuko,Kano, Kuniyuki,Omi, Jumpei,Inoue, Asuka,Aoki, Junken,Ohwada, Tomohiko
-
p. 9990 - 10029
(2020/10/18)
-
- Synthesis and enantiospecific analysis of enantiostructured triacylglycerols containing n-3 polyunsaturated fatty acids
-
The stereospecific structure of triacylglycerols (TAGs) affects the bioavailability of fatty acids. Lack of enantiopure reference compounds and effective enantiospecific methods have hindered the stereospecific analysis of individual TAGs. Twelve novel enantiostructured AAB-type TAGs were synthesized containing one of the three n-3 polyunsaturated fatty acid: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) in sn-1 or sn-3 position. These compounds formed six enantiomer pairs, which were separated with recycling high-performance liquid chromatography using chiral columns and UV detection. The chromatographic retention behavior of the enantiomers and the stereospecific elution order were studied. The enantiomer with an n-3 PUFA in the sn-1 position eluted faster than the enantiomer with the n-3 PUFA in the sn-3 position, regardless of the carbon chain length and number of double bonds of the PUFA. TAG enantiomers containing DHA exhibited highly different retention on the chiral column and were separated after the first column, whereas recycling was needed to separate the enantiomer pairs containing ALA or EPA. The system using two identical columns and one mobile phase, without sample derivatization, proved to be very effective also for peak purity assessment, confirming the enantiopurity of the synthesized structured TAGs being higher than 98 percent (96 percent ee).
- Gudmundsson, Haraldur G.,Haraldsson, Gudmundur G.,Kallio, Heikki,Kalpio, Marika,Linderborg, Kaisa M.,Magnússon, Jóhann D.,Yang, Baoru
-
-
- Stereoselective synthesis of the head group of archaeal phospholipid PGP-Me to investigate bacteriorhodopsin-lipid interactions
-
Phosphatidylglycerophosphate methyl ester (PGP-Me), a major constituent of the archaeal purple membrane, is essential for the proper proton-pump activity of bacteriorhodopsin (bR). We carried out the first synthesis of the bisphosphate head group of PGP-M
- Cui, Jin,Kawatake, Satoshi,Umegawa, Yuichi,Lethu, Sbastien,Yamagami, Masaki,Matsuoka, Shigeru,Sato, Fuminori,Matsumori, Nobuaki,Murata, Michio
-
supporting information
p. 10279 - 10284
(2015/10/28)
-
- Synthesis of enantiopure structured triacylglycerols
-
The synthesis of nine enantiopure structured triacylglycerols (TAGs) of the AAB type is described, all possessing the (S)-absolute configuration. Six of them possess one saturated and two identical unsaturated fatty acyl chains, whereas the remaining three possess two identical saturated fatty acids along with one unsaturated fatty acid. The former group was synthesized by a five-step chemoenzymatic route involving a highly regioselective immobilized Candida antarctica lipase, starting from enantiopure (R)-solketal. The second group was prepared by a fully chemical five-step approach based on the same chiral precursor. Such enantiopure TAGs are strongly required as standards for the enantiospecific analysis of intact TAGs in fats and oils.
- Kristinsson, Bjoern,Linderborg, Kaisa M.,Kallio, Heikki,Haraldsson, Gudmundur G.
-
p. 125 - 132
(2014/02/14)
-
- SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND PHARMACEUTICAL USE OF SAME AS HIV INTEGRASE INHIBITOR
-
Provided is a substituted spiropyrido[1,2-a]pyrazine derivative or a pharmaceutically acceptable salt thereof, which is useful as an anti-HIV agent. The present invention relates to a compound represented by the following formula [I] or [II] or a pharmace
- -
-
Paragraph 1547; 1548; 1549
(2014/08/19)
-
- Optically active monoacylglycerols: Synthesis and assessment of purity
-
Despite their simple structures, synthesis of 1(or 3)-acyl-sn-glycerols remains a challenge that cannot be ignored because of facile acyl migrations, which not only complicate the synthesis but also make direct GC or HPLC analysis unfeasible. Assessment of the optical purity of monoacylglycerols has, to date, relied almost exclusively on specific rotation data, which are small in value and thus insensitive to impurities. Now, a simple means to "magnify" the small specific rotations has been found, along with practical methods for the measurement of both 1,2-and 1,3-acyl migrations, which offer a convenient and straightforward alternative to Mori's NMR analysis of Mosher esters. With the aid of these methods, a range of conditions for deacetonide removal were examined en route to the synthesis of two natural monoacylglycerols. Refined hydrolysis conditions, along with useful knowledge about the solubility and reactivity of substrates with an ultra long alkyl chain are also presented. Copyright
- Chen, Chao-Yuan,Han, Wei-Bo,Chen, Hui-Jun,Wu, Yikang,Gao, Po
-
p. 4311 - 4318
(2013/07/26)
-
- Total synthesis of an immunomodulatory phosphoglycolipid from thermophilic bacteria
-
A method for the stereocontrolled synthesis of a bacterial phosphoglycolipid (PGL1) isolated from thermophilic bacteria is described. The key features of the synthesis include a highly α-selective glycosylation reaction between a trichloroacetimidate donor and a D-lyxose-derived primary alcohol acceptor and the late-stage incorporation of the phospholipid. Copyright
- Lin, Hong-Jyune,Adak, Avijit Kumar,Reddy, L. Vijaya Raghava,Wu, Shih-Hsiung,Lin, Chun-Cheng
-
p. 7989 - 7998
(2013/07/19)
-
- Synthesis of boron cluster lipids: Closo-dodecaborate as an alternative hydrophilic function of boronated liposomes for neutron capture therapy
-
(Chemical Equation Presented) We succeeded in the synthesis of the double-tailed boron cluster lipids 4a-c and 5a-c, which have a B 12H11S moiety as a hydrophilic function, by S-alkylation of B12H11SH (BSH) with bromoacetyl and chloroacetocarbamate derivatives of diacylglycerols for a liposomal boron delivery system on neutron capture therapy. Calcein encapsulation experiments revealed that the liposomes, prepared from the boron cluster lipid 4b, DMPC, PEG-DSPE, and cholesterol, are stable at 37°C in FBS solution for 24 h.
- Lee, Jong-Dae,Ueno, Manabu,Miyajima, Yusuke,Nakamura, Hiroyuki
-
p. 323 - 326
(2008/02/03)
-
- Synthesis of archaeal bipolar lipid analogues: A way to versatile drug/gene delivery systems
-
(Chemical Equation Presented) A synthetic route for the preparation of symmetrical and unsymmetrical archaeal tetraether-like analogues has been described. The syntheses are based upon the elaboration of hemimacrocyclic tetraether lipid cores from versati
- Brard, Mickaelle,Laine, Celine,Rethore, Gildas,Laurent, Isabelle,Neveu, Cecile,Lemiegre, Loic,Benvegnu, Thierry
-
p. 8267 - 8279
(2008/03/12)
-
- Self-assembled nanoreactors as highly active catalysts in the hydrolytic kinetic resolution (HKR) of epoxides in water
-
CoIII(salen) complexes have been immobilized on amphiphilic block copolymers, which self-assemble in water to give micellar aggregates with a hydrophobic Co(salen) core and a water-soluble shell (see picture). These aggregates were used to catalyze the hydrolytic kinetic resolution (HKR) of racemic aromatic epoxides over four consecutive cycles and gave the epoxides in up to 99 % ee. H2salen = N,N′-bis(salicylidene)ethylenediamine. (Chemical Equation Presented).
- Rossbach, Benjamin M.,Leopold, Kerstin,Weberskirch, Ralf
-
p. 1309 - 1312
(2007/10/03)
-
- Conversion of Epoxides to 1,3-Dioxolanes Catalyzed by Tin(II) Chloride
-
Anhydrous tin(II) chloride is an efficient catalyst for the reaction of epoxides with acetone to prepare 2,2-dimethyl-1,3-dioxolanes (acetonides) in good to excellent yields. Mono-, di-, and trisubstituted epoxides participate equally well in this diastereospecific reaction. The use of single enantiomer epoxides under the reported conditions results in significant erosion of optical activity.
- Vyvyan, James R.,Meyer, Jennifer A.,Meyer, Korin D.
-
p. 9144 - 9147
(2007/10/03)
-
- Compounds comprising sulfated nonulonic acid having antiviral activity
-
In order to provide the anti-retrovirus active compound with low anti-coagulant action and low cytotoxicity, compounds comprising glycoside or the salt thereof wherein lipid is linked to position 2 of sialic acid having all hydroxyl groups at positions 4,
- -
-
-
- Synthesis of lipophilic aldehydes and study of their inhibition effect on human digestive lipases.
-
[reaction: see text] Novel inhibitors of human digestive lipases, aldehyde dialkyl and alkyl-acyl glycerol analogues, were developed. The inhibitors were prepared starting from 3-(benzyloxy)-1,2-propanediol. The inhibition of human pancreatic and gastric lipases by the aldehyde derivatives was studied using the monolayer technique. (1R)-1-[(Dodecyloxy)methyl]-4-oxobutyl decanoate caused a 50% decrease in HPL and HGL activities at 0.100 and 0.053 molar fractions, respectively.
- Kotsovolou, Stavroula,Verger, Robert,Kokotos, George
-
p. 2625 - 2628
(2007/10/03)
-
- Structural determination of sulfoquinovosyldiacylglycerol by chiral syntheses
-
Chiral sulfoquinovosyldiacylglycerols (SQDGs) have been synthesized to determine the absolute stereochemistry and the biological activities. The 1 H NMR spectrum of a natural SQDG is comparable to that of synthetic (2S)-SQDG rather than that of the (2R) analogue. The biological activity of the respective isomers for DNA polymerase α and β inhibition was not distinguishable in the enzymatic assay.
- Hanashima, Shinya,Mizushina, Yoshiyuki,Yamazaki, Takayuki,Ohta, Keisuke,Takahashi, Shunya,Koshino, Hiroyuki,Sahara, Hiroeki,Sakaguchi, Kengo,Sugawara, Fumio
-
p. 4403 - 4407
(2007/10/03)
-
- Synthesis and triplex forming properties of an acyclic N7-glycosylated guanine nucleoside
-
A chiral acyclic nucleoside, one in which the ribose carbohydrate has been replaced with a glycerol-based linker, is prepared by glycosylating guanine at the N7-nitrogen. The stereochemically pure derivative is converted to a DMT-protected phosphoramidite for incorporation into DNA sequences. Sequence containing the acyclic N7-dG nucleoside are capable of forming DNA triplexes in which it is likely that the N1-H and N2-amino groups of the N7-dG are involved in recognition of the guanine base in G-C base pairs.
- St. Clair, Aimee,Xiang, Guobing,McLaughlin, Larry W.
-
p. 925 - 937
(2007/10/03)
-
- A cytosine analogue containing a conformationally flexible acyclic linker for triplex formation at sites with contiguous G-C base pairs
-
Two nucleoside derivatives of the pyrimidine bases T and m(5ox)C have been prepared with flexible acyclic carbohydrate linkers. A new procedure, beginning with (R)-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol permits the preparation of the stereochemically pure acyclic derivatives of both protected nucleoside analogues without contamination by a problematic rearrangement product. By simply increasing the flexibility of the carbohydrate portion of the am(5ox)C nucleoside derivative. 15-mer triplexes containing five contiguous G-C base pairs exhibit a 7-8 °C increase in T(m) value.
- Xiang, Guobing,McLaughlin, Larry W.
-
p. 375 - 392
(2007/10/03)
-
- The efficient synthesis of mixed diacyl phospholipids with polyunsaturated fatty acid in sn-2 position of glycerol
-
A convenient method for synthesis of the mixed-diacyl phospholipid using boron trichloride as an efficient reagent for the removal of benzyl protecting group from polyunsaturated diacylglycerols without affecting the double bond and acyl migration is desc
- Xia, Jie,Hui, Yong-Zheng
-
p. 3019 - 3021
(2007/10/03)
-
- Structure and Synthesis of Petrosynes, New Acetylenic Enol Ether Glycerides from the Okinawan Marine Sponge of the Genus Petrosia
-
Acetylenic enol ether glycerides, 1 and 3, were found in the Okinawan marine sponge of the genus Petrosia.The plane structures of these glycerides were deduced from spectroscopic analysis.Their complete structures were established by enantioselective total synthesis of all possible stereoisomers using (R)-1-O-benzylglycerol and its (S)-enantiomer, prepared from D-mannitol and L-ascorbic acid, respectively, as chiral building blocks.The synthesis involves the palladium(0)-catalyzed coupling reaction of bromo enol ether 9 with enediyne 21 as a key step.It became evident from the synthesis that the natural product 1 consisted of a mixture of (7R,2'S)-24 (petrosyne Ia) and (7S,2'S)-24 (petrosyne Ib), and the natural product 3 consisted of a mixture of (7R,2'S)-28 (petrosyne IIa) and (7S,2'S)-28 (petrosyne IIb).
- Iguchi, Kazuo,Kitade, Makoto,Kashiwagi, Toshihiko,Yamada, Yasuji
-
p. 5690 - 5698
(2007/10/02)
-
- SYNTHESIS OF AN ETHYLENE GLYCOL CROSS-LINKED AMINO ACID
-
Synthesis of an ethylene glycol-containing amino acid, (2R,9S)-N2-Cbz-N9-Boc-2,9-diamino-4,7-dioxadecanedioic acid 1-phenacyl 10-methyl diester 1, was studied through direct alkylation of N-Boc-L-serine and through BF3-catalyzed ring
- Ho, Mengfei,Wang, Weiheng,Douvlos, Maria,Pham, Thuha,Klock, Timothy
-
p. 1283 - 1286
(2007/10/02)
-
- Synthesis and antiviral activity of the nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cystosine
-
The acyclic nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (2, HPMPC) was prepared on a multigram scale in 18% overall yield starting from (R)-2,3-O-isopropylideneglycerol. The key step in the nine-step synthetic route is coupling of cytosine with the side-chain derivative 8 which bears a protected phosphonylmethyl ether group. In vitro data showed that HPMPC has good activity against herpes simplex virus types 1 and 2, although it was 10-fold less potent that acyclovir [ACV, 9-[(2-hydroxyethoxy)methyl]guanine]. By comparison, HPMPC exhibited greater activity than ACV against a thymidine kinase deficient strain of HSV 1 and was more potent than ganciclovir [DHPG, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine] against human cytomegalovirus. In vivo, HPMPC showed exceptional potency against HSV 1 systemic infection in mice, having an ED50 of 0.1 mg/kg per day (ip) compared with 50 mg/kg per day for ACV. HPMPc was also more efficacious than ACV in the topical treatment of HSV 1 induced cutaneous lesions in guinea pigs.
- Bronson,Ghazzouli,Hitchcock,Webb II,Martin
-
p. 1457 - 1463
(2007/10/02)
-
- SYNTHESIS OF AXIALLY DISSYMMETRIC 3,5-OCTADIENE FRAMEWORK WITH C2 CHIRALITY VIA PALLADIUM(II)-CATALYZED TWOFOLD SIGMATROPIC REARRANGEMENT
-
Palladium(II)-catalyzed sigmatropic rearrangement of (4R,5R)-4,5-(bisacetoxy)-1,8-(bisbenzyloxy)-2(E),6(E)-octadiene has proceeded convergently to give (2S,7S)-2,7-(bisacetoxy)-1,8-(bisbenzyloxy)-3(E),5(E)-octadiene, translating the original chirality completely to the migration termini, which constitutes a novel synthesis of optically pure 3,5-octadiene with C2 chirality.
- Saito, Seiki,Hamano, Shin-ichi,Moriyama, Hiroshi,Okada, Keiji,Moriwake, Toshio
-
p. 1157 - 1160
(2007/10/02)
-